JSEQ_scRNAseq - supplement manager (Supp.1)

Advantage of the JSEQ/CSSG® tool in high-resolution cell population discovery

Supplement 1.1

Brain complexity

Warning! Below we presented data as both HTML interactive and pdf static plots. Since the data are large in some instances [e.g. cerebellum], the interactive version can not always load properly on some PCs. In such case, the pdf static may be used. If possible, we recommend using the Opera browser.

Cerebellum - mouse data

Data:

Normalized expression table

	Astrocytes Aqp4 Gpc5 - Apoe	Astrocytes Aqp4 Gpc5 - Tprkb	Astrocytes Slc1a3 Slc7a11 - Cped1	Astrocytes Slc1a3 Slc7a11 - Ranbp3l	Bergmann Gdf10 Gria1 - Gria1
Xkr4	0.2160268	0.2216736	0.2404465	0.4221899	0.7699403
Gm1992	0.0210700	0.0077600	0.0735336	0.0498822	0.1123058
Gm37381	0.0166807	0.0128804	0.0215986	0.0082632	0.0170091
Rp1	0.0498806	0.0614188	0.0074269	0.0249311	0.0491225
Sox17	0.0048606	0.0053718	0.0000000	0.0000000	0.0061107

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Cell composition

Subclasses [59] Interactive  Static

Subtypes [141] Interactive  Static

Motor cortex - mouse data

Data:

Normalized expression table

	Astrocytes Slc1a3 Apoe - Slc1a2	Astrocytes Slc1a3 Grin2c - Slc1a2	Astrocytes Slc1a3 Ptgds - Ptgds	Endothelial Cldn5 Flt1 - Bsg	GABAergic Npy Adarb2 - Grip1
Xkr4	2.717575	0.8348435	1.8546009	1.580576	6.8728476
Gm1992	0.000000	0.0191590	0.1427593	0.000000	0.2583325
Gm37381	0.000000	0.0237413	0.0000000	0.000000	0.0463138
Rp1	0.000000	0.0432075	0.0000000	0.000000	0.0453302
Sox17	0.000000	0.0000000	0.0000000	1.013113	0.0000000

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Cell composition

Subclasses [18] Interactive  Static

Subtypes [30] Interactive  Static

Auditory cortex - mouse data

Data:

Normalized expression table

	Astrocytes Slc1a3 Hepacam - Apoe	Astrocytes Slc1a3 Hepacam - Cst3	Astrocytes Slc1a3 Hepacam - Slc1a3	Astrocytes Slc1a3 Mertk - Gpc5	Astrocytes Slc1a3 Plpp3 - Apoe
Xkr4	3.4593642	3.1257874	3.006409	1.2922381	0.8926728
Gm1992	1.4871213	1.4236178	1.233734	0.0549860	0.1668951
Gm37381	0.0325659	0.0157422	0.000000	0.0000000	0.0000000
Rp1	0.0381125	0.0136421	0.000000	0.0131356	0.0000000
Sox17	0.0000000	0.0151990	0.000000	0.0000000	0.0000000

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Cell composition

Subclasses [28] Interactive  Static

Subtypes [52] Interactive  Static

Orbitofrontal cortex - mouse data

Data:

Normalized expression table

	Astrocytes Slc1a3 Car2 - Cd81	Astrocytes Slc1a3 Car2 - Glul	Astrocytes Slc1a3 Gpc5 - Gpc5	Astrocytes Slc1a3 Gpc5 - Slc1a3	Dopaminergic Rxfp1 Ntng2 - Ntng2
Xkr4	4.4754240	5.0894768	0.8558702	0.7277140	6.0490904
Gm1992	2.3226102	2.1724244	0.0320016	0.0000000	0.5854197
Gm37381	0.0385550	0.0517933	0.0082961	0.0000000	0.0000000
Rp1	0.0775233	0.0000000	0.0081012	0.0000000	0.0000000
Sox17	0.0000000	0.0550306	0.0081034	0.0855263	0.0000000

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Cell composition

Subclasses [25] Interactive  Static

Subtypes [39] Interactive  Static

Entorhinal cortex - mouse data

Data:

Normalized expression table

	Astrocytes Aqp4 Apoe - Apoe	Astrocytes Slc1a3 Brinp3 - Cdh18	Astrocytes Slc1a3 Brinp3 - Gpc5	Astrocytes Slc1a3 Brinp3 - Hs3st4	Astrocytes Slc1a3 Erbb4 - Cntnap2
Xkr4	0.8525836	5.4301929	4.8089745	5.3186612	6.0951426
Gm1992	0.3703344	3.0330123	2.2403751	2.1420419	3.5548043
Gm37381	0.0071477	0.0000000	0.0000000	0.0442252	0.0192348
Rp1	0.0101238	0.0667335	0.0538529	0.0000000	0.1012159
Sox17	0.0165821	0.0329424	0.0000000	0.0463407	0.0000000

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Cell composition

Subclasses [33] Interactive  Static

Subtypes [69] Interactive  Static

Hippocampus - mouse data

Data:

Normalized expression table

	Astrocytes Slc1a3 Plpp3 - Apoe	Astrocytes Slc1a3 Plpp3 - Cst3	Dopaminergic Cck Hs3st4 - Ptprd	Dopaminergic Rxfp1 4933413l06rik - Pex5l	GABAergic Npy Erbb4 - Erbb4
Xkr4	1.0848248	1.1714033	2.7680306	3.9451423	5.2902240
Gm1992	0.4413108	0.5016723	0.9104245	1.2229372	1.9764989
Gm37381	0.0000000	0.0711501	0.0000000	0.0897211	0.0000000
Rp1	0.1165463	0.0752031	0.0683943	0.0000000	0.1730269
Sox17	0.2134944	0.2914689	0.0000000	0.0000000	0.0000000

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Cell composition

Subclasses [12] Interactive  Static

Subtypes [23] Interactive  Static

Striatum - mouse data

Data:

Normalized expression table

	Astrocytes Slc1a3 Aqp4 - Clu	Astrocytes Slc1a3 Aqp4 - Slc1a2	Cholinergic Calb1 Slc5a7 - Acly	Cholinergic Tacr1 Npy - Tacr1	Endothelial Cldn5 Ly6c1 - Sparc
Xkr4	0.0000000	0.0000000	0.0000000	0.000000	0.0421118
Sox17	0.0000000	0.0000000	0.0000000	1.761456	1.9647710
Mrpl15	0.0000000	0.9133879	0.7388574	3.035198	0.5635974
Lypla1	0.9655279	0.7947375	0.0000000	4.204058	1.1343567
Tcea1	1.2686132	1.9388918	0.7489950	4.482223	1.5668944

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Cell composition

Subclasses [12] Interactive  Static

Subtypes [32] Interactive  Static

Thalamus - mouse data

Data:

Normalized expression table

	Dopaminergic Adcyap1 Uncx - Ndn	Dopaminergic Adcyap1 Uncx - Pitx2	Dopaminergic Lmx1a Uncx - Dmrta2	Endothelial Cldn5 Igfbp7 - Sparc	GABAergic Npy Asic4 - Gata3
Xkr4	0.0000000	0.0000000	0.000000	0.000000	0.0973496
Sox17	0.0000000	0.0000000	0.000000	1.989048	0.0000000
Mrpl15	1.3528010	1.5724406	2.255019	2.333679	1.7855451
Lypla1	0.9502086	0.2416054	0.435312	2.630886	1.0604708
Gm37988	0.0000000	0.0000000	0.000000	0.000000	0.0000000

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Cell composition

Subclasses [12] Interactive  Static

Subtypes [32] Interactive  Static

Hypothalamus - mouse data

Data:

Normalized expression table

	Astrocytes Slc1a3 Gja1 - Atp1b2	Astrocytes Slc1a3 Gja1 - Slc1a3	Astrocytes Slc1a3 Gja1 - Slc6a11	Endothelial Cldn5 Flt1 - Cldn5	Endothelial Cldn5 Flt1 - Itm2a
Xkr4	0.1478369	0.0000000	0.0000000	0.0389687	0.0426850
Gm1992	0.0000000	0.0000000	0.0000000	0.0000000	0.0000000
Rp1	0.0000000	0.0000000	0.0000000	0.0786196	0.0923171
Sox17	0.0000000	0.0217464	0.0000000	3.4246754	2.6691677
Mrpl15	0.4358399	0.5520658	0.4324584	0.6034894	0.8981087

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Cell composition

Subclasses [18] Interactive  Static

Subtypes [45] Interactive  Static

Brain organoids - human data

Data:

Normalized expression table

	Astrocytes AGT CCL2 - AGT	Astrocytes AQP4 HEPN1 - AQP4	GABAergic TAC3 DLX6-AS1 - SOX4	Glutamatergic SSTR2 RP11-93H24.3 - TUBA4A	NPCs FOXG1 C4ORF32 - C11ORF96
RP11-34P13.3	0.0000000	0.000000	0.0000000	0.000000	0.0000000
RP11-34P13.7	0.0000000	0.000000	0.0057023	0.000000	0.0000000
FO538757.2	2.5167939	1.393544	1.2805036	2.050920	2.1861439
AP006222.2	2.7259739	1.445707	0.5640264	1.171028	0.8439073
RP4-669L17.10	0.0286725	0.000000	0.0053284	0.000000	0.0000000

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Cell composition

Subclasses [22] Interactive  Static

Subtypes [157] Interactive  Static

Supplement 1.2

Cell subtypes function enrichment

Table of the cell subtypes (CSSG) gene function enrichment

Cell_name	Function_gene	biological_process	cellular_component	molecular_function
Astrocytes Slc1a3 Hepacam - Apoe	APOE	cholesterol metabolic process	extracellular space	amyloid-beta binding
Astrocytes Slc1a3 Hepacam - Cst3	CST3	defense response	extracellular space	amyloid-beta binding
Astrocytes Slc1a3 Hepacam - Slc1a3	SLC1A3	L-amino acid transport	plasma membrane	organic acid:sodium symporter activity
Astrocytes Slc1a3 Mertk - Gpc5	GPC5	protein localization to membrane	cell surface	protein binding
Astrocytes Slc1a3 Plpp3 - Apoe	APOE	cholesterol metabolic process	extracellular space	amyloid-beta binding

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Enrichment_tool GEDSpy

Supplement 1.3

AD-related genes analysis

Supplement 1.3.1

Distrubution of AD-related genes in mouse brain and human brain organoids

The relative expression range for each gene in every region was estimated separately

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Supplement 1.3.2

Table of AD-related gene deregulated expression in the cell subtypes

cell_names	p_Apoe	subclass_DE_Apoe	global_DE_Apoe	region
GABAergic Sst Nxph1 - Grip1 -> GABAergic Sst Nxph1 - Kcnmb2	0.8399968	-0.0543533	-0.0055550	auditory_cortex
GABAergic Sst Nxph1 - Kcnmb2 -> GABAergic Sst Nxph1 - Grip1	0.8399968	0.0543533	0.0487983	auditory_cortex
GABAergic Vip Adarb2 - Adarb2 -> GABAergic Npy Adarb2 - Erbb4	0.0518980	0.3750681	0.1325001	auditory_cortex
GABAergic Npy Adarb2 - Erbb4 -> GABAergic Vip Adarb2 - Adarb2	0.0518980	-0.3750681	-0.2425680	auditory_cortex
Glutamatergic Cck Tox - Pex5l -> Glutamatergic Cck Tox - Malat1	0.0000000	-1.1674819	-0.8746888	auditory_cortex

p - p-value of Wilcoxon-Test between local subtypes within an initial cluster, subclass_DE - direct deregulated expression (DE) [explained in Methods: Supplementary analysis] between the subtype and each local subtype within an initial cluster, global_DE - direct deregulated expression between the subtype and each global subtypes separately for every region/structure

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Disclaimer

The analysis was performed by the non-profit and open-source AI/ML JSEQ/CSSG pipeline. More information is available on GitHub. In case of further questions, please contact us. The JSEQ® was created in the Department of Molecular Neurobiology, Institute of Bioorganic Chemistry, Polish Academy of Sciences.

JSEQ® source

Graphical source

Brain structures:

• Allen Brain Explorer® [http://connectivity.brain-map.org/3d-viewer?v=1]

Human brain organoids:

• Own source of Department of Molecular Neurobiology, Institute of Bioorganic Chemistry, Polish Academy of Sciences